Urea cycle disorders are characterized by a defect in the urea cycle resulting in the accumulation of ammonia and its precursor amino acids. Citrullinemia (ASD) and argininosuccinic acidemia (ALD) are two of the urea cycle disorders. Citrullinemia is caused by a defect in the urea cycle enzyme argininosuccinic acid synthetase. Deficiency of this enzyme results in markedly elevated blood ammonia, citrulline and glutamine levels, as well as urine citrulline and orotic acid and decreased arginine production.
Argininosuccinic acidemia is caused by a defect in the production of the urea cycle enzyme argininosuccinase. Deficiency in this enzyme results in markedly elevated blood ammonia, citrulline and glutamine levels, as well as urine argininosuccinic acid. Elevations of argininosuccinic acid are not found in blood due to its efficient excretion by the kidneys.
Clinical symptoms of citrullinemia and argininosuccinic acidemia become apparent between 1 and 3 days of age, when the newborn undergoes a rapid neurological deterioration. As ammonia levels increase, newborns quickly develop anorexia, vomiting, hypothermia, irritability, lethargy, seizures, apnea and cerebral edema. Without intervention, they become comatose and die.
Gout is precipitation of monosodium uric acid crystals into tissue, usually in and around joints, most often causing recurrent acute or chronic arthritis. The initial attack of acute arthritis is usually monarticular and often involves the 1st metatarsophalangeal joint. Symptoms include acute pain, tenderness, warmth, redness, and swelling. Diagnosis requires identification of crystals in synovial fluid.
Managing acute pathology of often relies on the addressing underlying pathology and symptoms of the disease. There is currently a need in the art for new compositions to treatment of moderate to severe urea cycle disorders and gout.